Vascular Abnormalities in Mice Lacking the Endothelial Gap Junction Proteins connexin37 and connexin40

摘要

Cellswithinthevascularwallarecoupledbygapjunctions,allowingfordirectintercellulartransferoflowmolecularweightmolecules.Althoughgapjunctionsarebelievedtobeimportantforvasculardevelopmentandfunction,theirpreciserolesarenotwellunderstood.Micelackingeitherconnexin37(Cx37)orconnexin40(Cx40),thepredominantgapjunctionproteinspresentinvascularendothelium,areviableandexhibitphenotypesthatarelargelynon-bloodvesselrelated.SinceCx37andCx40arecoexpressedinendothelialcellsandcouldoverlapfunctionally,somerolesofjunctionalcommunicationmayonlyberevealedbytheeliminationofbothconnexins.Inthisstudy,weinterbreedCx37andCx40knockoutmicetogenerateCx37a?’/a?’Cx40a?’/a?’animalsandshowthattheydisplayseverevascularabnormalitiesanddieperinatally.Cx37a?’/a?’Cx40a?’/a?’animalsexhibitlocalizedhemorrhagesinskin,testis,gastrointestinaltissues,andlungs,withpronouncedbloodvesseldilatationandcongestionoccurringinsomeareas.Vascularanomalieswereparticularlystrikingintestisandintestine.Intestis,abnormalvascularchannelswerepresent,withthesechannelscoalescingintoacavernous,endothelium-linedbloodpoolresemblingahemangioma.Theseresultsprovideevidenceofacriticalroleforendothelialgapjunction-mediatedcommunicationinthedevelopmentand/orfunctionalmaintenanceofsegmentsofthemousevasculature.